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Background and Objective: Oral submucous fibrosis (OSMF) is a well-known premalignant condition encountered in Indian population. Although the disease is advancing rapidly, its reliable treatment modality for its various stages has not yet evolved. The aim of the present study is to compare the effect of newer antioxidant lycopene with a placebo in conjunction with the cessation of causative habit in the treatment of OSMF. Materials and Methods: The study group included 92 patients with OSMF. The OSMF diagnosis was established through a composite of accepted clinical and histopathological characteristics. Out of 92, 46 patients were given lycopene and remaining 46 were on placebo drug. Lycopene group patients received 8 mg Lycored TM per day in two divided doses of 4 mg each, while placebo group patients received placebo tablet twice a day. Patients were examined for changes in mouth opening and other clinical symptoms of OSMF during three months and were followed up for next two months. Results: Lycopene was found to be significantly efficacious in the amelioration of signs and symptoms of OSMF. It was effective in reducing the objective signs of OSMF as demonstrated by the improved maximal mouth opening, percentage of which was 69.56%(P<0.05). Interpretation and Conclusion: Reactive oxygen compounds or free radicals have been implicated as one of the major harmful factors for premalignant and malignant conditions. Present study concludes that lycopene, a newer antioxidant, appears to be a very promising drug in the management of OSMF.

The fifth chapter of the upcoming fifth edition of the 2022 World Health Organization Classification of Tumours of the Head and Neck titled Tumours of the oral cavity and mobile tongue, has had some modifications from the 2017 fourth edition. A new section \"Non-neoplastic Lesions\", introduces two new entries: necrotizing sialometaplasia and melanoacanthoma. The combined Oral potentially malignant disorders and Oral epithelial dysplasia section in the 2015 WHO has now been separated and submucous fibrosis and HPV-associated dysplasia are also discussed in separate sections. Carcinoma cuniculatum and verrucous carcinoma are described in dedicated sections, reflecting that the oral cavity is the most common location in the head and neck for both these entities which have distinct clinical and histologic features from conventional squamous cell carcinoma. This review summarizes the changes in Chapter 5 with special reference to new additions, deletions, and sections that reflect current clinical, histological, and molecular advances.

Oral submucous fibrosis (OSF), characterized by excessive deposition of extracellular matrix (ECM) that causes oral mucosal tissue sclerosis, and even cancer transformation, is a chronic, progressive fibrosis disease. However, despite some advancements in recent years, no targeted antifibrotic strategies for OSF have been approved; likely because the complicated mechanisms that initiate and drive fibrosis remain to be determined. In this review, we briefly introduce the epidemiology and etiology of OSF. Then, we highlight how cell-intrinsic changes in significant structural cells can drive fibrotic response by regulating biological behaviors, secretion function, and activation of ECM-producing myofibroblasts. In addition, we also discuss the role of innate and adaptive immune cells and how they contribute to the pathogenesis of OSF. Finally, we summarize strategies to interrupt key mechanisms that cause OSF, including modulation of the ECM, inhibition of inflammation, improvement of vascular disturbance. This review will provide potential routes for developing novel anti-OSF therapeutics.

Oral submucous fibrosis (OSMF) is a high-risk premalignant condition predominantly seen in the Indian subcontinent. The aim of the present study was to evaluate the efficacy of oxitard capsules in the management of OSMF. Total of 120 subjects with clinico-pathologically diagnosed OSMF were included in the study and divided equally in 2 groups; Group A (oxitard group) and Group B (placebo group). Group A was administered 2 oxitard capsules twice daily and Group B was given placebo tablets twice daily, for 3 months. Evaluation for different clinical parameters was done at regular intervals and data was analyzed using the Student's paired t test and Chi-square test. P < 0.001 was considered to be statistically significant. Clinical improvements in mouth-opening and tongue protrusion were significant in the Group A (P < 0.001). Subjective symptoms of burning sensation (P = 0.0001), pain associated with the lesion (P = 0.000), difficulty in swallowing (P = 0.0003) and speech (P = 0.0005) also significantly improved in the Group A. There was a mild to moderate decrease in the size of the lesion. Though there is no definitive treatment for the condition; however, oxitard capsules can bring about significant clinical improvements in the symptoms like mouth-opening, tongue protrusion, burning sensation, difficulty in swallowing and speech and pain associated with the lesion, thereby improving the quality of life of the affected individuals.

Objectives The aim of the study was to compare the effectiveness of vasodilator isoxsuprine to dexamethasone with hyaluronidase injections and physiotherapy in the treatment of oral submucous fibrosis. Materials and methods Forty patients with oral submucous fibrosis were randomly assigned into three groups. Group A patients ( n  = 15) received 10 mg isoxsuprine tablets four times per day, group B ( n  = 15) biweekly dexamethasone with hyaluronidase intralesional injections, and group C ( n  = 10) placebo tablets. In addition, all patients were instructed physiotherapy exercises. The treatment time was 6 weeks and patients were followed-up for 4 months thereafter. The effect of the treatment was evaluated by measurements of inter-incisal distance and oral burning sensation and evaluation of histological findings of the diseased mucosa. Results Mouth opening increased and burning sensation decreased significantly in all groups, but the effects were significantly greater in groups receiving either oral isoxsuprine or dexamethasone with hyaluronidase injections in addition to physiotherapy. The decrease in burning sensation occurred more rapidly in patients receiving intralesional dexamethasone with hyaluronidase. Histological improvement was not observed in any of the groups. Conclusions Oral isoxsuprine as well as dexamethasone with hyaluronidase injections combined to physiotherapy alleviate symptoms of oral submucous fibrosis significantly more efficiently than physiotherapy alone. Clinical relevance Oral isoxsuprine can be considered as a new candidate drug for the treatment of oral submucous fibrosis. Physiotherapy exercises provide relief of symptoms and should be instructed to all patients.

In South and Southeast Asia, the habit of chewing betel nuts is prevalent, which leads to oral submucous fibrosis (OSF). OSF is a well‐established precancerous lesion, and a portion of OSF cases eventually progress to oral squamous cell carcinoma (OSCC). However, the specific molecular mechanisms underlying the malignant transformation of OSCC from OSF are poorly understood. In this study, the leading‐edge techniques of Spatial Transcriptomics (ST) and Spatial Metabolomics (SM) are integrated to obtain spatial location information of cancer cells, fibroblasts, and immune cells, as well as the transcriptomic and metabolomic landscapes in OSF‐derived OSCC tissues. This work reveals for the first time that some OSF‐derived OSCC cells undergo partial epithelial–mesenchymal transition (pEMT) within the in situ carcinoma (ISC) region, eventually acquiring fibroblast‐like phenotypes and participating in collagen deposition. Complex interactions among epithelial cells, fibroblasts, and immune cells in the tumor microenvironment are demonstrated. Most importantly, significant metabolic reprogramming in OSF‐derived OSCC, including abnormal polyamine metabolism, potentially playing a pivotal role in promoting tumorigenesis and immune evasion is discovered. The ST and SM data in this study shed new light on deciphering the mechanisms of OSF‐derived OSCC. The work also offers invaluable clues for the prevention and treatment of OSCC. Betel nut chewing is linked to the development of OSF and, in severe cases, OSCC. Employing spatial multi‐omics technology, this study unveils the malignant progression of OSCC cells, intricate cell‐to‐cell interactions, and the identification of abnormal polyamine metabolism in OSF‐derived OSCC. These findings offer novel insights into the underlying mechanisms of OSCC.

Oral submucous fibrosis (OSF) is a chronic oral condition with a potential for malignant transformation. This study aims to investigate the correlation between DNA aneuploidy and dysproliferative lesions in OSF using DNA image cytometry to provide insights into cancer risk assessment. The study included patients diagnosed with OSF, OSF combined with oral leukoplakia (OLK), OSF that progressed to oral squamous cell carcinoma (OSCC), and healthy controls. Exfoliated oral mucosal cells were collected and analyzed using DNA image cytometry. Statistical analyses were conducted using SPSS 22.0 to compare the results across different groups. The study revealed that DNA image cytometry demonstrated high sensitivity and specificity for diagnosing OSCC and epithelial dysplasia. Furthermore, the frequency of abnormal DNA content in oral exfoliated cells from patients with OSF + OLK significantly increased with the grade of abnormal histopathological epithelial proliferation. Significant differences in DNA content were observed between the OSF, OSF + OLK, and OSCC groups. Additionally, patients with OSF showed no significant difference in DNA content between the buccal and tongue mucosae, but those with OSF + OLK demonstrated differences in DNA content between the OSF and OLK lesion areas. DNA image cytometry is a valuable tool for assessing cancer risk in OSF patients, particularly those with coexisting OLK. The findings suggest that OSF + OLK patients have a higher risk of cancer than those with OSF alone, providing crucial scientific evidence for predicting cancer risk and guiding early intervention strategies.

Oral submucous fibrosis (OSF) is a chronic, progressive, and fibrotic condition of the oral mucosa that carries an elevated risk of malignant transformation. We aimed to identify and validate novel genes associated with the regulation of epithelial-to-mesenchymal transition (EMT) in OSF. Genes regulating EMT were identified through differential gene expression analysis, using a LogFC threshold of -1 and + 1 and a padj value < 0.05, based on data from GEO datasets and the TCGA-HNSC datasets. The curated EMT genes were correlated with functional cancer states and subjected to clustering to identify candidate genes. Integration of bioinformatics and proteomics led to the discovery of the EMT genes MMP9 , SPARC , and ITGA5 as novel candidates. Comprehensive pathway and immunohistochemical analyses confirmed their roles in regulating EMT in OSF, oral squamous cell carcinoma (OSCC), and OSF-associated squamous cell carcinoma (OSFSCC). The significant roles of MMP9 , SPARC , and ITGA5 in fibrosis and malignancy suggest a novel mechanism in which fibrosis-associated type 2 EMT undergoes transition to type 3 EMT, driving OSF towards malignancy.

Oral submucosal fibrosis (OSF) is a chronic, progressive and potentially malignant oral disorder with a high regional incidence and malignant rate. With the development of the disease, the normal oral function and social life of patients are seriously affected. This review mainly introduces the various pathogenic factors and mechanisms of OSF, the mechanism of malignant transformation into oral squamous cell carcinoma (OSCC), and the existing treatment methods and new therapeutic targets and drugs. This paper summarizes the key molecules in the pathogenic and malignant mechanism of OSF, the miRNAs and lncRNAs with abnormal changes, and the natural compounds with therapeutic effects, which provides new molecular targets and further research directions for the prevention and treatment of OSF.

Betel quid (BQ) chewing increased the risk of oral cancer and oral submucous fibrosis (OSMF), an oral premalignant disorder (OPMD) with malignant transformation potential. BQ components such as areca nut (AN), trauma by coarse AN fiber, catechin, copper, alkaloids, stimulated reactive oxygen species (ROS), inflammation and cytotoxicity are suggested to be the contributing factors. They may induce tissue inflammation, proliferation of fibroblasts and collagen deposition, myofibroblast differentiation and contraction, collagen cross-links and inhibit collagen phagocytosis, finally leading to the development of OSMF and oral cancer. These events are mediated by BQ components-induced changes of extracellular matrix (ECM) turnover via regulation of TGF-β1, plasminogen activator inhibitor-1 (PAI-1), cystatin, lysyl oxidase (LOX) and tissue inhibitors of metalloproteinases (TIMPs) and metalloproteinases (MMPs). Genetic susceptibility is also involved in these disease processes. Further understanding the molecular mechanisms of BQ-induced OSMF and oral cancer can be helpful for future disease prevention and treatment.